Cloning of the murine c-fgr proto-oncogene cDNA and induction of c-fgr expression by proliferation and activation factors in normal bone marrow-derived monocytic cells.
Cloning of the murine c-fgr proto-oncogene cDNA and induction of c-fgr expression by proliferation and activation factors in normal bone marrow-derived monocytic cells.
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作者：
Yi Tl;Willman Cl
发现正常小鼠骨髓来源的单核细胞含有原癌基因酪氨酸激酶src家族的两个成员c-fgr和hck的转录本。虽然HCK转录本仅在细菌脂多糖(LPS)刺激下增加，但c-FGR的表达在单核/巨噬细胞增殖性刺激CSF-1以及激活单核细胞进入功能状态的信号(粒细胞-巨噬细胞集落刺激因子(GM-CSF)、脂多糖和干扰素)的瞬时诱导下均可表达。这些数据表明，这些高度相关的酪氨酸激酶可能不同地介导不同的单核/巨噬细胞刺激的影响；特别是c-FGR原癌基因，它在正常细胞中选择性地在单核细胞中表达，可能在这些细胞中发挥关键的功能作用。从经CSF-1刺激的骨髓来源的单核细胞的RNA文库中分离到一个2.2kb的cDNA克隆，该克隆包含一个1551碱基的开放阅读框，编码一种具有蛋白酪氨酸激酶特征的蛋白质。该克隆与v-FGR同源性最高，可能编码正常单核细胞表达的小鼠c-FGR转录本。然而，与以前报道的来自EBV转化的B细胞和异种外周血细胞的c-FGR序列相比，来自正常小鼠单核细胞的c-FGR基因在序列上与蛋白质氨基末端的12-62位氨基酸有显著差异，这可能介导了src蛋白酪氨酸激酶家族的底物特异性和亚细胞定位。
Normal murine bone marrow-derived monocytic cells were found to contain transcripts for c-fgr and hck, two members of the src family of proto-oncogene tyrosine kinases. While hck transcripts were increased only in response to bacterial lipopolysaccaride (LPS), expression of c-fgr was transiently induced both by the monocyte/macrophage proliferative stimulus CSF-1 as well as by signals which activate monocytic cells to functional states (granulocyte-macrophage colony stimulating factor (GM-CSF), LPS, and gamma interferon). These data suggest that these highly related tyrosine kinases may differentially mediate the effects of distinct monocyte/macrophage stimuli; and, that the c-fgr proto-oncogene in particular, which in normal cells is selectively expressed in monocytes, may play a pivotal functional role in these cells. A 2.2 kb cDNA clone, containing a 1551 base pair open reading frame encoding a protein with all of the hallmarks of a protein-tyrosine kinase, was isolated from a cDNA library made from RNA of CSF-1-stimulated bone marrow-derived monocytic cells. This clone had the highest homology to v-fgr and likely encodes the murine c-fgr transcript expressed by normal monocytes. However, when compared to sequences previously reported for human c-fgr derived from EBV-transformed B cells and heterogeneous peripheral blood cells, the c-fgr cDNA derived from normal murine monocytic cells differed significantly in sequence from amino acids 12-62 in the amino terminal domain of the protein which may mediate the substrate specificity and subcellular location of the src family of protein-tyrosine kinases.